UNSW Embryology

Musculoskeletal Development - Mesoderm/Somite

© Dr Mark Hill (2008)

Acknowledgements

Introduction

This page looks at early mesoderm development, in particular the differentiation of paraxial mesoderm into the somite. The somite is a developmental feature that extabishes a rostrocaudal segmantal body plan of axial musculoskeletal elements.

Page Links: Introduction | Some Recent Findings | Mesoderm Development | Somite Development | Stage 13/14 Embryo Somites | Formation of Vertebra | Limbs | Glossary | References

Some Recent Findings

Juliane Feller, Andre Schneider, Karin Schuster-Gossler, and Achim Gossler Noncyclic Notch activity in the presomitic mesoderm demonstrates uncoupling of somite compartmentalization and boundary formation Genes Dev. 2008;22 2166-2171

"Embryos expressing activated Notch (NICD) formed up to 18 somites. Expression in the presomitic mesoderm (PSM) of Hes7, Lfng, and Spry2 was no longer cyclic, whereas Axin2 was expressed dynamically. NICD expression led to caudalization of somites, and loss of Notch activity to their rostralization. Thus, segmentation and anterior–posterior somite patterning can be uncoupled, differential Notch signaling is not required to form segment borders, and Notch is unlikely to be the pacemaker of the segmentation clock."

Wasteson P, Johansson BR, Jukkola T, Breuer S, Akyürek LM, Partanen J, Lindahl P. Developmental origin of smooth muscle cells in the descending aorta in mice. Development. 2008 May;135(10):1823-32. (More? Cardiovascular System - Blood Vessels)

"Aortic smooth muscle cells (SMCs) have been proposed to derive from lateral plate mesoderm. ....(these results) suggested that all SMCs in the adult descending aorta derive from the somites, whereas no contribution was recorded from lateral plate mesoderm."

Kahane N, Ben-Yair R, Kalcheim C. Medial pioneer fibers pattern the morphogenesis of early myoblasts derived from the lateral somite. Dev Biol. 2007 Feb 28; [Epub ahead of print]

"...we propose that medial pioneers are needed for proper morphogenesis of the lateral population which is kept as undifferentiated mesenchyme by BMP4 until their arrival. In addition, medial pioneers also organize dermomyotome lip-derived fibers suggesting that they have a general role in patterning myotome development."

(More? Somite Development References)

Mesoderm Development

	Cells migrate through the primitive streak to form mesodermal layer. Extraembryonic mesoderm lies adjacent to the trilaminar embryo totally enclosing the amnion, yolk sac and forming the connecting stalk.
	Paraxial mesoderm accumulates under the neural plate with thinner mesoderm laterally. This forms 2 thickened streaks running the length of the embryonic disc along the rostrocaudal axis. In humans, during the 3rd week, this mesoderm begins to segment. The neural plate folds to form a neural groove and folds.
	Segmentation of the paraxial mesoderm into somites continues caudally at 1 somite/90minutes and a cavity (intraembryonic coelom) forms in the lateral plate mesoderm separating somatic and splanchnic mesoderm.
	Somites continue to form. The neural groove fuses dorsally to form a tube at the level of the 4th somite and "zips up cranially and caudally and the neural crest migrates into the mesoderm.  Next Somite Development     Note these are very simplified figures.

Somite Development

		Mesoderm beside the notochord (axial mesoderm) thickens, forming the paraxial mesoderm as a pair of strips along the rostro-caudal axis. Paraxial mesoderm towards the rostral end, begins to segment forming the first somite. Somites are then sequentially added caudally. The somitocoel, is a cavity forming in early somites, which is lost as the somite matures.
		Cells in the somite differentiate medially to form the sclerotome (forms vertebral column) and laterally to form the dermomyotome. The dermomyotome then forms the dermotome (forms dermis) and myotome (forms muscle).
		Pig Embryo Serial Sections (st13/14) Serial section D3 (rotated 90 degrees) Mouseover to identify structures see also links below
The myotome differentiates to form 2 components dorsally the epimere and ventrally the hypomere, which in turn form epaxial and hypaxial muscles respectively. The bulk of the trunk and limb muscle coming from the Hypaxial mesoderm. Different structures will be contributed depending upon the somite level.  Note these are very simplified figures.

Stage 13/14 Embryo Somites

G5: Tangential section through the lower curvature of the embryo (neural tube cut twice). Newly formed somites containing somitocoeles and consisting of dark, lateral dermomyotomes and more diffuse, medial sclerotomes. Notochord. Amnion and amniotic cavity.

Due to the development of somites in a rostrocaudal sequence, these somites are relatively and observably more immature (formed later) than those seen in D1-D3 below.

D1: The somite development overview (on page 1) shows this organization rotated 90^o

D2:

D3:

Surface bulge of a somite, either side of neural tube. Somites at this level have spread from their original ball shape.

• Somite components
  • dermatome- dark region lying directly under surface ectoderm.
  • myotome- slightly paler colour beneath dermatome.
  • sclerotome- very pale region surrounding notocord and between neural tube and dorsal aorta.
• Notochord- dark spot ventral to neural tube.
• Paired dorsal aortae, giving segmental branches.
• Inferior cardinal veins (lateral, empty). Dorsal root ganglion- dark patches either side of neural tube.
• Spinal nerve passing between sclerotome and myotome.
• Neural tube- note the alar and basal laminae of cells, sulcus limitans.

(sections from level of lung buds to stomach)

Axial Skeleton - Vertebrae

(See also below notes on vertebral development )

G7: Cervical region: dark masses of dorsal root ganglia. Lumbar region: dorsal aorta with its dorsal segmental arterial branches. Between each dorsal segmental artery is a darker-staining mass of mesenchyme (the dark part of a sclerotome) which is the anlage of the intervertebral disc. The dorsal segmenta lartery itself marks the location of the centre of the light-staining part of the sclerotome, which is the future vertebral body. The dark band dorsal to the sclerotomes is the basal lamina of the wall of the neural tube.

G6: Cervical region (neural tube cut very obliquely): note the wavy notochord and thin roof and floor plates. Thoracic region: alternating light and dark parts of the sclerotomes (vertebral bodies and I.V. Discs, respectively). Lumbar region: tiny, dorsal segmental branches of dorsal aorta Each little branch is aligned almost parallel to the cranial border of the next caudal dorsal root ganglion (segmented dark masses). Sacral region: oblique section of neural tube, notochord.

Formation of Vertebra

The vertebra of the spinal cord go through a lengthy period of maturation which I have briefly summarized below. A key aspect of development for vertebra (spinal cord) and skull (brain) is to create a flexible enclosure to allow continued growth of the neural components (that are relatively immature).

Precartilaginous Stage (Human wk4 - wk6) (shown in stage 13/14 embryo)

• generated by the sclerotomal mesenchyme surrounding the notochord
• vertebra form out of register with the original somites
• each sclerotome has 2 components
  • cranial loose cells (fuses with next cranial segment)
  • caudal dense cells (upper part of which forms annulus fibrosus of intervertebral disc (IVD); lower part fuses with next caudal segment (cranial+caudal=centrum)
• notochord forms nucleus pulposus (surrounded by sclerotomal annulus fibrosus) of IVD

Cartilaginous Stage (Human wk6 -)

• chondrification centers form in mesenchyme of centrum
• replaces mesenchyme with cartilage

Bony Stage (Human wk7 - 25 years) (shown in stage 22 embryo)

• primary ossification centers form in cartilage
  • 2 dorsal- each vertebral arch
  • 1 ventral- centrum
• at birth vertebra is these 3 boney parts connected by cartilage
• postnatally 3-5 years- arch fuses
• puberty- secondary ossification centers form on body and facets

References: Kusumi K, Turnpenny PD. Formation errors of the vertebral column. J Bone Joint Surg Am. 2007 Feb;89 Suppl 1:64-71.

Limbs

Upper Limb

D3: Cranial edge of forelimb fold (future shoulder region). Note the superolateral extent of the coelomic serosa with respect to the limb fold.

D4,D5: Note axillary fossa appearing on each side and local thickening of the ectoderm in the region of the fossa. Note thinnest ectoderm stretched over heart and neural tube.

D6-D7: Limb folds and fossae. Greatest thickening of the ectoderm is at apex of the limb fold: the apical ectodermal ridge. The mesenchyme of the limb is densest under the ectoderm. Note the narrow distance between the ectoderm of the axillary fossa and the serosa of the body cavity. The limb fold has distinct flexor and extensor surfaces: the flexor surface is narrower and has thicker ectoderm. Note blood vessels close to flexor surface

Lower Limb

E1-E3: Note blood vessels in limb fold mesenchyme, and pale-staining nerves at root of limb (E1).

E4: Spinal nerves (part of future brachial plexus) directed towards the flexor side of the limb fold. Note also the section of the lumbosacral region with neural tube and hindlimb bulge.

E5-E7: Hindlimb fold. Forelimb fold.

F1,F2: Caudal limit of forelimb. Broad extensor surface. Dense mesenchyme of hindlimb. Note lumbar somites, somitocoeles.

Stage 13/14 Embryo (Pig)

A1	A2	A3	A4	A5	A6	A7
B1	B2	B3	B4	B5	B6	B7
C1	C2	C3	C4	C5	C6	C7
D1	D2	D3	D4	D5	D6	D7
E1	E2	E3	E4	E5	E6	E7
F1	F2	F3	F4	F5	F6	F7
G1	G2	G3	G4	G5	G6	G7

References

Note - See also other specific musculoskeletal notes pages: References | Abnormalities | Limb | Axial Skeleton | Skull | Bone | Human Bone | Skeletal Muscle | Molecular

Reviews

Baron R, Rawadi G, Roman-Roman S. Wnt signaling: a key regulator of bone mass. Curr Top Dev Biol. 2006;76:103-27.

Pogue R, Lyons K. BMP signaling in the cartilage growth plate. Curr Top Dev Biol. 2006;76:1-48.

Articles

Juliane Feller, Andre Schneider, Karin Schuster-Gossler, and Achim Gossler Noncyclic Notch activity in the presomitic mesoderm demonstrates uncoupling of somite compartmentalization and boundary formation Genes Dev. 2008;22 2166-2171

Wasteson P, Johansson BR, Jukkola T, Breuer S, Akyürek LM, Partanen J, Lindahl P. Developmental origin of smooth muscle cells in the descending aorta in mice. Development. 2008 May;135(10):1823-32.

Nissim S, Allard P, Bandyopadhyay A, Harfe BD, Tabin CJ. Characterization of a novel ectodermal signaling center regulating Tbx2 and Shh in the vertebrate limb. Dev Biol. 2006 Dec 9;

Search PubMed: May 2008 "somite development" 1,745 reference articles of which 159 were reviews.

Search PubMed Now: somite development | somite

(More? PubMed- Medline)

Selected Lists of References from PubMed March 1999 search results are available for Department of Anatomy computers without internet access: Somite Reviews | Somitogenesis Abstracts | Mesoderm Review List

Glossary of Terms

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Quick Links

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